This project, entitled Mapping Early Network Dysfunction in FTD and AD will develop novel network connectivity analyses with the goal of improving early detection and diagnosis of frontotemporal dementia (FTD) and Alzheimer's disease (AD). Normal cognitive and behavioral functions require coordinated activity, within large-scale, distributed networks. Emerging data from human studies and animal disease models suggest that specific networks may develop early, tell-tale aberrations during incipient neurodegenerative disease. To explore this possibility, we will use functional connectivity MRI (fcMRI) and diffusion spectral imaging (DSI) to study 60 patients with FTD, 20 asymptomatic FTD gene mutation carriers, 15 patients with AD, and 30 healthy controls. We hypothesize that network connectivity mapping will link each clinical syndrome to a specific intrinsic brain network, will prove capable of detecting early disease, and will provide new insights into symptom pathogenesis. Our aims are (1) to detect network alterations in early stage FTD and AD, (2) to compare the ability of fcMRI, DSI, and conventional structural MRI to detect network-level dysfunction in presymptomatic FTD gene mutation carriers, and (3) to correlate FTD and AD symptoms with network connectivity disruption. The knowledge gained could provide a first step toward a novel, non- invasive imaging biomarker for early FTD and AD and clarify the network basis for FTD, AD, and other neuropsychiatric disorders that target the brain at the network level. RELEVANCE (See instructions): This project will investigate the specific brain networks disrupted in frontemporal dementia and Alzheimer's disease. The goal of the research is to use neuroimaging to clarify where in the brain these diseases begin and how network dysfunction leads to symptoms. Further developed, these methods could improve early detection and diagnosis and provide a sensitive biomarker for following the effects of treatment.